X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia (XMEN) syndrome is an inborn error of immunity caused by loss-of-function (LOF) mutations in the magnesium transporter gene (MAGT1).
To describe clinical and laboratory findings of 2 siblings (P) with XMEN syndrome and no chronic EBV infection.
Two males, P1 (19 years old) and P2 (17 years old). Maternal uncle with common variable immunodeficiency (CVID) at 21 years who died of diffuse large B cell lymphoma. P1: Follow-up since 3 years old for recurrent wheezing, respiratory infections, and regular weight/height progression. P2: Previously healthy, consulted at 16 years due to 3-month-term fever, bilateral cervical lymphadenopathy, weight loss, and asthenia. Biopsy confirmed classical Hodgkin lymphoma. Positive blood EBV IgG and negative EBV PCR in blood and lymph nodes biopsy. Immunological evaluation showed panhypogammaglobulinemia in P1. Impaired protein/pneumococcal response, increased frequency of CD4+ central memory T cells with high activation markers, severe impairment of B cell compartment, and high transitional B cells with decreased total memory B cell (IgM and switched memory B lymphocyte) in both patients. While P1 was diagnosed with CVID and started monthly intravenous immunoglobulin (IVIG), P2 began chemotherapy and IVIG treatment. No variants in SH2D1A gene. Almost absent NKG2D in CD8+ and natural killer cells in both patients. Molecular study identified absence of MAGT1 gene transcripts and confirmed a hemizygous deletion encompassing exons 9 and 10 in both patients and the mother as a heterozygous carrier. Follow-up: P1 presented chronic onychomycosis and respiratory infections. P2 presented a relapse of his lymphoma and received haploidentical hematopoietic stem cell transplantation with his mother.
XMEN disease should be considered as a differential diagnosis in male patients presenting with a CVID-like phenotype and malignancy, even in the absence of chronic EBV infection, due to its heterogeneous clinical presentation and significant impact on immune function.
